T Cells Expressing a Bispecific CAR Targeting CS1 and BCMA in Relapsed/Refractory Multiple Myeloma

NCT04662099 | Unknown Phase 1

• 1 other identifier: CS1+BCMA bispecific CART
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, single-arm study to evaluate the safety and efficacy of the bispecific CAR T cells targeting CS1 and BCMA in patients with relapsed or refractory multiple myeloma.

Conditions

CS1+ or BCMA+ Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-related Adverse Events

  Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).

  within 2 years after infusion

Secondary Outcomes (2)

• Overall response rate(ORR) and complete response rate(CRR) of administering T cells Expressing a bispecific CAR Targeting CS1 and BCMA in Relapsed/Refractory Multiple Myeloma

  2 years after infusion

• Overall survival(OS), duration of Response(DOR), progress-free survival(PFS) of administering T cells Expressing a bispecific CAR Targeting CS1 and BCMA in Relapsed/Refractory Multiple Myeloma

  2 years after infusion

Other Outcomes (1)

• In vivo expansion and survival of CS1&BCMA bispecific CAR T cells

  2 years after infusion

Study Arms (1)

Conditioning chemotherapy plus CAR T cells infusion

EXPERIMENTAL

Biological: Conditioning chemotherapy followed by CAR T cell infusion

Interventions

Conditioning chemotherapy followed by CAR T cell infusion BIOLOGICAL

Conditioning chemotherapy: Cyclophosphamide 250 mg/m\^2 and fludarabine 30 mg/m\^2 IV infusion on days -5, -4, and -3 CAR T cells infusion: 0.75x10\^6-3.0X10\^6 CAR+ T cells per kg of recipient bodyweight. if DLTs don't occur at the dose of 3.0X10\^6 CAR+ T cells per kg, the investigators will discuss whether to try higher dose.

Conditioning chemotherapy plus CAR T cells infusion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Each potential subject must meet all of the following criteria to be enrolled in the study:
• Aged 18-78 years old, males or females.
• Relapsed or refractory multiple myeloma according to IMWG diagnostic criteria.
• Received at least 2 prior lines of treatment for multiple myeloma, including a proteasome inhibitor and an immunomodulatory drug.
• Detectable MM cells in bone marrow by conventional morphologic methods or flow cytometry, and positive expression of CS1 or BCMA on MM cells as confirmed by immunohistochemistry or flow cytometry.
• Measurable diseases at screening as defined by any of the following:
• Serum M-protein level ≥1.0g/dL;
• Urine M-protein level ≥200mg/24 hours;
• Serum immunoglobulin free light chain(FLC) ≥10 mg/dL provided abnormal FLC ratio.
• Recovery to grade 1 or baseline of toxicities due to prior treatment, excluding hematologic toxicities and toxicity of no clinical significance, like alopecia.
• ECOG Performance Status 0 \~ 2 (ECOG status of larger than 2 points caused by MM osteolytic destruction is accepted).
• Good organ function at screening as defined by any of the following:
• AST and ALT ≤ 2.5×upper limit of normal (ULN);
• Total bilirubin≤ 2.0×ULN;
• Creatinine clearance ≥30 mL/min/1.73m2;

You may not qualify if:

• Any potential subject who meets any of the following criteria will be excluded from participating in the study:
• Evidence of serious viral, bacterial, or uncontrolled systemic fungal infection.
• Seropositive for human immunodeficiency virus (HIV) antibody.
• Seronegative for hepatitis B antigen or a known history of hepatitis B.
• Hepatitis C (anti-hepatitis C virus \[HCV\] antibody positive or HCV-RNA quantitation positive) or a known history of hepatitis C.
• Systemic corticosteroid therapy of greater than 5 mg/day of prednisone or equivalent dose within 2 weeks prior to apheresis.
• Active autoimmune disease or a history of autoimmune disease within 3 years.
• The following cardiac conditions: Myocardial infarction or coronary artery bypass graft ≤6 months prior to enrollment; History of clinically significant ventricular arrhythmia or unexplained; New York Heart Association stage III or IV congestive heart failure.
• A history of epilepsy or other central nervous system diseases or altered mental status.
• Known life-threatening allergies, hypersensitivity, or intolerance to CAR-T cells or relevant lymphodepleting regimens (cyclophosphamide and fludarabine).
• Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within one year after receiving study treatment.
• Any uncontrolled diseases, other than multiple myeloma, that may lead to abnormal death.
• Being participating in other intervention studies.
• Other cases excluded by the Investigators.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Wuhan Si'an Medical Technology Co., Ltd: collaborator

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Related Publications (3)

• Zah E, Nam E, Bhuvan V, Tran U, Ji BY, Gosliner SB, Wang X, Brown CE, Chen YY. Systematically optimized BCMA/CS1 bispecific CAR-T cells robustly control heterogeneous multiple myeloma. Nat Commun. 2020 May 8;11(1):2283. doi: 10.1038/s41467-020-16160-5.

  PMID: 32385241 BACKGROUND

• Mikkilineni L, Kochenderfer JN. CAR T cell therapies for patients with multiple myeloma. Nat Rev Clin Oncol. 2021 Feb;18(2):71-84. doi: 10.1038/s41571-020-0427-6. Epub 2020 Sep 25.

  PMID: 32978608 BACKGROUND

• Li C, Xu J, Luo W, Liao D, Xie W, Wei Q, Zhang Y, Wang X, Wu Z, Kang Y, Zheng J, Xiong W, Deng J, Hu Y, Mei H. Bispecific CS1-BCMA CAR-T cells are clinically active in relapsed or refractory multiple myeloma. Leukemia. 2024 Jan;38(1):149-159. doi: 10.1038/s41375-023-02065-x. Epub 2023 Oct 17.

  PMID: 37848634 DERIVED

Study Officials

• Heng Mei, M.D., Ph.D

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heng Mei, M.D., Ph.D

CONTACT

86-13986183871; hmei@hust.edu.cn

Chenggong Li

CONTACT

86-18868112136; chenggongli@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Proferssor, Cheif Doctor

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 10, 2020
• Study Start: March 25, 2020
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: August 16, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)